title: Etanercept decreases the innate immune wounding response in psoriasis.
abstract: Cathelicidin is increased when normal skin is injured and in psoriasis lesions where it has been suggested to play a pivotal role in inflammation through interactions with self-DNA and toll-like receptor 9 (TLR-9) in keratinocytes and plasmacytoid dendritic cells. Because of etanercept's success in treating psoriasis, we hypothesized that etanercept may suppress TLR-9 and cathelicidin induction. Examination of experimentally induced wounds of psoriatic lesional and non-lesional skin, and comparison with wounded normal skin, shows that the induction of cathelicidin and TLR-9 is greatly enhanced in lesional psoriatic skin. Six weeks of etanercept appears not to affect the baseline expression of cathelicidin or TLR-9, but does blunt the induction of cathelicidin in psoriasis with wounding. These findings support the role of cathelicidin in the enhancement of local inflammation in psoriasis and may partially explain one of the mechanisms enabling TNF-α inhibitors to successfully treat this disorder.
authors.affiliation: Division of Dermatology, Department of Medicine, University of California, San Diego, CA 92093, USA.
authors.forename: Tissa R
authors.initials: TR
authors.lastname: Hata
authors.forename: Maryam
authors.initials: M
authors.lastname: Afshar
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Miller
authors.forename: Aimee M
authors.initials: AM
authors.lastname: Two
authors.forename: Paul
authors.initials: P
authors.lastname: Kotol
authors.forename: Michelle
authors.initials: M
authors.lastname: Jackson
authors.forename: Doru T
authors.initials: DT
authors.lastname: Alexandrescu
authors.forename: Filamer
authors.initials: F
authors.lastname: Kabigting
authors.forename: Monika
authors.initials: M
authors.lastname: Gerber
authors.forename: Yuping
authors.initials: Y
authors.lastname: Lai
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gallo
mesh_terms: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000096:biosynthesis; D000068800:Etanercept; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007074:Immunoglobulin G / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D011565:Psoriasis / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D051217:Toll-Like Receptor 9 / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D000068800:Etanercept
keywords: TLR-9; cathelicidin; etanercept; psoriasis